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目的探讨11β-HSD1抑制剂H8对db/db小鼠胰岛素敏感性的影响。方法实验动物40只分成5个组,每组8只,分别是db/db对照组(Dia组)、罗格列酮组(Ros组)、姜黄素组(Cur组)、姜黄素类似物H8组(H8组)、db/m对照组(Con组)。H8灌胃给药42 d后尾静脉采血检测葡萄糖耐量(OGTT)、胰岛素耐量(IPITT);在第0、1、3、6周尾静脉采血检测空腹血糖值;眼球取血检测胰岛素抵抗系数(HOM A-IR);酶学检测肝脏、脂肪中11β-HSD1活性;ELISA法检测血清中糖皮质激素水平。结果 OGTT结果显示,与Dia组相比较,Ros组和H8组各时间点血糖值均有所降低;IPITT结果显示,相对于Dia组,Ros组和H8组血糖值均有所下降;空腹血糖在给药后第1~6周,H8组与Dia组比较明显降低;与Dia组比较,Ros组、Cur组和H8组胰岛素抵抗指数(HOMA-RI)明显降低(P<0.001);与Dia组对比,H8组可以明显的抑制肝脏(P<0.01)和脂肪(P<0.01)中11β-HSD1的活性;与Dia组对比,H8组GC水平降低(P<0.001)。结论 11β-HSD1的抑制剂H8可以降低db/db小鼠肝脏GC水平,进而提高胰岛素的敏感性。
Objective To investigate the effect of 11β-HSD1 inhibitor H8 on insulin sensitivity in db / db mice. Methods Forty experimental rats were divided into five groups (n = 8 each): db / db control group (Dia group), rosiglitazone group (Ros group), curcumin group (Cur group), curcumin analogue H8 Group (H8 group), db / m control group (Con group). Blood samples were taken from the tail vein of H8 for 24 d to measure the glucose tolerance (OGTT) and insulin tolerance (IPITT). Blood samples were taken from tail vein at 0, 1, 3 and 6 weeks to detect fasting blood glucose (FBG) HOM A-IR); 11β-HSD1 activity in liver and fat was detected by enzymology; glucocorticoid level in serum was detected by ELISA. Results OGTT results showed that compared with Dia group, Ros group and H8 group at each time point blood glucose levels were reduced; IPITT results showed that relative to the Dia group, Ros group and H8 group blood glucose values have decreased; fasting blood glucose in Compared with Dia group, the HOMA-RI of Ros group, Cur group and H8 group were significantly decreased (P <0.001), compared with Dia group Compared with Dia group, GC in H8 group decreased significantly (P <0.001) .Conclusion: H8 can significantly inhibit the activity of 11β-HSD1 in liver (P <0.01) and adipose tissue (P <0.01). Conclusion Hβ, an inhibitor of 11β-HSD1, can reduce the hepatic GC level in db / db mice and further improve the insulin sensitivity.